ACSM5

Chr 16

acyl-CoA synthetase medium chain family member 5

ACSM5 encodes an enzyme that catalyzes the activation of fatty acids by CoA to produce acyl-CoA, the first step in fatty acid metabolism within mitochondria. Mutations cause autosomal recessive spastic paraplegia-56, which involves progressive spasticity and weakness primarily affecting the lower limbs. This gene shows low constraint against loss-of-function variants, consistent with recessive inheritance patterns.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.26
Clinical SummaryACSM5
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.26LOEUF
pLI 0.000
Z-score 0.40
OE 0.92 (0.691.26)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.62Z-score
OE missense 1.10 (1.001.19)
367 obs / 335.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.92 (0.691.26)
00.351.4
Missense OE1.10 (1.001.19)
00.61.4
Synonymous OE1.23
01.21.6
LoF obs/exp: 29 / 31.4Missense obs/exp: 367 / 335.0Syn Z: -2.11
DN
0.6743th %ile
GOF
0.6053th %ile
LOF
0.4037th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ACSM5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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